TRANSNEURONAL SIGNALS FOR AFFERENT REGULATION

传入活动已被证明可以调节神经的许多特性

Afferent activity has been shown to regulate a number of properties of postsynaptic neurons. It is well known that afferent input regulates the electrical activity of postsynaptic neurons through the action of neurotransmitters. Afferent input, however, also regulates the metabolic activity of postsynaptic neurons, particularly early in development. The signals for this latter form of transneuronal regulation are not known. The brain stem auditory system of the chick has proven to be a useful system for investigation transneuronal regulation of cellular metabolism. Second-order auditory neurons in nucleus magnocellularis (NM, the cochlear nucleus) receive their sole excitatory input from the ipsilateral auditory nerve. Elimination of activity in the auditory nerve on one side of the brain has been shown to alter a number of properties of NM neurons. For example, after a couple of days, a portion of the neurons in NM die and the rest shrink in size. Early after the elimination of auditory nerve activity in young chicks, changes in metabolism in NM neurons have been observed. For example, within 1 hour, there is a dramatic decrease in protein synthesis by NM neurons on the ipsilateral side of the brain. Such changes in NM neurons structure and function, however, are not observed after elimination of auditory nerve activity in adult birds. The proposed experiments investigate the signals involved in the regulation of both the electrical activity and metabolic activity of NM neurons. These experiments will be carried out on both young (1-2 week old) and adult (1 year old) chickens. Regulation of electrical activity is investigated first by analyzing the anatomical distribution of different classes of excitatory amino acid receptors. The physiological effects of excitatory amino acids are then assessed by application of specific agonists and antagonists while recording intracellularly from NM neurons in an in vitro brain slice preparation. Metabolic regulation is investigated by assessing changes in protein synthesis in the in vitro slice preparation after various treatments. Unilateral stimulation of the auditory nerve in vitro has been shown to produce similar changes in protein synthesis as those observed in vivo. Application of specific agonists and antagonists will assess the relative roles of different types of excitatory amino acid receptors and second messenger systems in transneuronal regulation of brain stem auditory system, 2) an understanding of the signals responsible for the regulation of neuronal metabolism in this system and 3) an understanding of age-related differences which may account for the age- dependence in the sensitivity of neurons to alterations of afferent activity.